PROJECT SUMMARY Tuberculosis (TB) is an important disease globally and remains a threat to the United States. In some parts of South Africa nearly 1% of the population develops TB disease annually, partly because of the very high rates of HIV infection in that country, an infection that makes people susceptible to secondary infection by TB. The way in which the body resists TB via the immune response is only partly understood, which creates difficulty in understanding what properties a new vaccine against TB should have. Furthermore the body's own immune response inadvertently can make TB worse by reacting strongly to parts of the bacterium responsible. A collaboration between a leading basic Science group at the National Institutes of Health (NIH) and a group of researchers in South Africa was therefore funded two years' ago. The aim is to investigate in humans recent findings in the mouse model that have the potential to improve our understanding and thus prevent and treat TB. We are assembling groups of TB patients from whom samples of blood and from the disease site will be made available. We will also track the progress of the patients during TB antibiotic treatment. We will use the materials from the patients to test several ideas that have arisen from NIH. Another aspect contributing to tuberculosis in South Africa is the legacy of apartheid: a policy that sought to segregate people of differing colors and associated with discrimination in all aspects of life such as housing, education and employment. Although South Africa became fully democratic in 1994, reversing the years of discrimination and providing opportunity to all is a long process. This revision program will specifically apply additional funding to provide educational opportunities via our research to scientists at two historically disadvantaged universities in South Africa: Walter Sisulu University and Sefako Makgatho Health Sciences University. Through these studies and additional opportunities, this collaborative project will improve understanding of people's immune response to TB, enhancing our ability to tackle this devastating condition more effectively. In addition the revision program promises the chance to provide research training for previously underrepresented persons, thus increasing and distributing more equitably the expertise to conduct highly relevant public health research.